Abstract CFAR, the Core Facility for Aged Rodents, has been a major feature of the University of Michigan Claude Pepper Center since its inception in 1989. CFAR will continue to serve the needs of Pepper Center investigators through four Specific Aims. Aim 1: We will continue work initiated in the previous five years on four varieties of mice: (a) Mice lacking PAPP-A, a protease that controls IGF-1 availability; (b) Mice overexpressing Syntaxin-4, a modulator of insulin sensitivity; (c) Mice in which p16-positive (senescent) cells can be pharmacologically deleted at adult ages; and (d) Mice treated by linagliptin, a modulator of post- prandial glucose spikes. Aim 2: We will develop new mouse models based on amino acid restriction, which follows our previous demonstration of slow aging and delayed disease in mice given limiting amounts of dietary methionine. Aim 3: We will explore the role of juvenile, adult, and liver-specific growth hormone responses to four drugs that extend mouse lifespan, specifically the TOR inhibitor rapamycin, the diabetic drug acarbose, the non-feminizing steroid 17-?-estradiol, and the anti-inflammatory agent NDGA. Aim 4: We will select one or two new mouse models per year, through collaboration with UM scientists, pilot project awardees, and colleagues at other research universities, for initial discovery research on questions related to the biology of aging, emphasizing interventions that alter metabolism and inflammation in ways that postpone late life illnesses and disabilities.